scholarly journals Castration induces antiapoptotic effects during myocardial regional ischemia reperfusion

2018 ◽  
Vol 6 (4) ◽  
pp. 379-388
Author(s):  
Najah R Hadi ◽  
Fadhil Al-amran
Keyword(s):  
Sham Group ◽  
Troponin I ◽  
Ischemia Reperfusion ◽  
Male Rat ◽  
Control Group ◽  
Regional Ischemia ◽  
Rat Hearts ◽  
Tnf Α ◽  
Heart Injury

Restoration of blood flow to ischemic myocardium results in the ischemia reperfusion (I/R) injury. This study was undertaken to investigate the potential role of endogenous testosterone in the regional ischemia reperfusion and apoptosis of the male rat hearts. Rats underwent surgical ligation of LAD and subjected to ischemia for 25 min and reperfusion for 40 min, and 2nd underwent surgical castration, left 3wks for recovery, then underwent surgical LAD ligation. Blood samples were collected from the heart for measurement of plasma level of cardiac troponin I (cTn-I). The hearts were harvested, and divided into 3 sections, the 1st for the measurement of cardiac apoptosis level, the 2nd homogenized for measurement of tissue (TNF-α, IL1-β, ICAM-1) and the 3rdwas fixed in 10% formalin for histological examination. Compared with the sham group, levels of tissue TNF-α & IL-1β, ICAM-1 and apoptosis; plasma cTn-I were increased (P<0.05) in the control group, all control group rats showed significant myocardial injury (P<0.05) compared with the sham group. Castration significantly counteracts the increase in myocardial levels of TNF-α, IL-1, ICAM-1, plasma cTn-I and apoptosis (P<0.05). Histological analysis revealed that castration markedly reduced (P<0.05) the severity of the heart injury in the rats underwent the regional ischemia-reperfusion procedure. This study reveals that surgical castration may ameliorate regional I/R injury and apoptosis in the ischemic heart in rats.

scholarly journals Antiapoptotic Effect of Simvastatin Ameliorates Myocardial Ischemia/Reperfusion Injury

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Najah R. Hadi ◽  
Fadhil Al-amran ◽  
Maitham Yousif ◽  
Suhaad T. Zamil
Keyword(s):  
Coronary Artery ◽  
Sham Group ◽  
Troponin I ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Interleukin 1 ◽  
Vehicle Group ◽  
Control Group ◽  
Albino Rats ◽  
Regional Ischemia

Background. Myocardial ischemial reperfusion represents a clinically relevant problem associated with thrombolysis, angioplasty, and coronary bypass surgery. Injury of myocardium due to ischemial reperfusion includes cardiac contractile dysfunction, arrhythmias, and irreversible myocytes damage. These changes are considered to be the consequence of imbalance between the formation of oxidants and the availability of endogenous antioxidants in the heart. Objective. This study was undertaken to investigate the potential role of Simvastatin in the amelioration of myocardial I/R injury induced by ligation of coronary artery in a rat model. Materials and Methods. Adult male Swiss Albino rats were randomized into 4 equal groups. Group (1): sham group: rats underwent the same anesthetic and surgical procedures as those in the control group except ligation of LAD coronary artery, group (2): control group: rats were subjected to regional ischemia for 25 min and reperfusion for 2 hours by ligation of LAD coronary artery, group (3): control vehicle group: rats received vehicle of Simvastatin (normal saline) via IP injection and were subjected to regional ischemia for 25 min and reperfusion for 2 hours by ligation of LAD coronary artery, group (4): Simvastatin treated group: rats were pretreated with Simvastatin 1 mg/kg i.p. 1 hr before ligation of LAD coronary artery. At the end of experiment (2 hr of reperfusion), blood samples were collected from the heart for the measurement of plasma level of cardiac troponin I (cTnI). After that the heart was harvested and divided into 3 parts; one part was used for measurement of apoptosis, another part was homogenized for the measurement of tissue tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1α, and the last part for histopathology study. Results. Compared with the sham group, levels of myocardial TNF-α and IL-1β, IL-6, MCP-1, and MIP-1α and plasma cTnI were increased (P<0.05). Histologically, all rats in control group showed significant (P<0.05) cardiac injury. Furthermore, all rats in control group showed significant (P<0.05) apoptosis. Simvastatin significantly counteracted the increase in myocardium level of TNF-α, IL-1B, IL-6, MCP-1 and MIP-1α, plasma cTnI, and apoptosis (P< 0.05). Histological analysis revealed that Simvastatin markedly reduced (P< 0.05) the severity of heart injury in the rats that underwent LAD ligation procedure. Conclusions. The results of the present study reveal that Simvastatin may ameliorate myocardial I/R injury in rats via interfering with inflammatory reactions and apoptosis which were induced by I/R injury.

Abstract 385: Amelioration of Heart Transplantation-Induced Ischemia-Reperfusion Injury by Melatonin and Ghrelin in Rats

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Fadhil Alamran
Keyword(s):  
Heart Transplantation ◽  
Sham Group ◽  
Troponin I ◽  
Ischemia Reperfusion ◽  
Graft Function ◽  
Control Group ◽  
Inflammatory Reactions ◽  
Heterotopic Heart Transplantation ◽  
Tnf Α ◽  
Transplant Procedure

Background: Global myocardial ischemia reperfusion (I/R), which is often obligatory during cardiac surgery, induce an inflammatory response in the transplanted heart. Inflammatory reactions in the graft have a pivotal influence on acute as well as long term graft function. Objective: This study was undertaken to investigate the potential role of melatonin and ghrelin in amelioration of I/R injury in the transplanted heart in rat model. Materials and Methods: The rats were randomized into 4 equal groups. Group 1 sham group, rat underwent the same anesthetic and surgical procedure as the control group except for heterotopic heart transplantation, group 2 control group, rats underwent heterotopic heart transplantation and subjected to global ischemia for 30 min and reperfusion for 2 hours, group 3 donor and recipient rats received melatonin 10 mg/kg i.p. 30 min before the transplant procedure and the same dose at the reperfusion, group 4 donor and recipient rats received ghrelin 10 -8 mol/kg i.p. ( 2 doses) 13 & 1 hour before the transplant procedure, the heterotopic heart transplantation is done using the cuff technique in the neck ( the aorta of the donor is anastomosed with the carotid artery of the recipient and the pulmonary artery of the donor to the jugular vein of the recipient). At the end of experiment (2 hr of reperfusion), blood samples were collected from the heart for measurement of plasma level of cardiac troponin I(cTn I). The heart were harvested, the apical side was fixed in 10% formalin for histological examination and the basal side was homogenized for the measurement of tissue tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and intracellular adhesion molecule-1 (ICAM-1). Results: Compared with the sham group, levels of myocardial TNF-α & IL-1β, and ICAM-1; plasma cTn I were increased (p<0.05), Histologically, all induced untreated rats showed significant myocardial injury ( P < 0.05) Both melatonin and ghrelin significantly counteract the increase in myocardium level of TNF-α, IL-1, & ICAM-1 ( P < 0.05). histological analysis revealed that both melatonin and ghrelin markedly reduced ( P < 0.05) the severity of heart injury in the rats underwent transplant procedure. Conclusion: The results of the present study reveal that melatonin and ghrelin may ameliorate I/R injury in the grafted heart in rats via interfering with inflammatory reactions which induced by I/R injury . These findings suggested that both melatonin and ghrelin have a promising graft protective effect against transplant induced global I/R injury.

scholarly journals Irbesartan ameliorate inflammatory responses, and apoptosis induced by myocardial ischemia/reperfusion in male rats

2019 ◽  
Vol 7 (2) ◽  
pp. 138-150
Author(s):  
Najah R. Hadi ◽  
Fadhil G. Al-Amran
Keyword(s):  
Myocardial Ischemia ◽  
Troponin I ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion ◽  
Cardiac Injury ◽  
Male Rats ◽  
Control Group ◽  
Inflammatory Reactions ◽  
Tnf Α ◽  
Myocardial Ischemia Reperfusion

Myocardial ischemia–reperfusion (I-R) represents a clinically relevant problem associated with thrombolysis, angioplasty and coronary bypass surgery. This study was undertaken to investigate the potential role of Irbesartan in amelioration of myocardial I/R injury induced by ligation of coronary artery (LAD) in a rat model. We are pretreated the animals with Irbesartan 3mg/kg i.p. 30 minutes before ligation of LAD. At the end of experiment (2 h of reperfusion), blood samples were collected from the heart for measurement of plasma level of cardiac troponin I (cTn-I). Compared with the sham group, levels of myocardial TNF-α, IL-1β, IL-6, MCP-1, MIP-1 alpha, and plasma cTn-I were increased (P<0.05). Histologically, all rats in control group showed significant cardiac injury after I-R. Furthermore, rats in control group showed significant apoptosis. Irbesartan significantly counteract the increased in myocardium level of TNF-α, IL-1B, IL-6, MCP-1, MIP-1 alpha, plasma cTn-I and apoptotosis (P<0.05). Histological analysis revealed that Irbesartan markedly reduced the severity of heart injury in the rats underwent LAD ligation procedure. We concluded that Irbesartan may ameliorate myocardial I/R injury in rats via interfering with inflammatory reactions and apoptosis which induced by I/R injury.

scholarly journals CircHIPK3 regulates the autophagy and apoptosis of hypoxia/reoxygenation-stimulated cardiomyocytes via the miR-20b-5p/ATG7 axis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Zhimei Qiu ◽  
Yan Wang ◽  
Weiwei Liu ◽  
Chaofu Li ◽  
Ranzun Zhao ◽  
...  
Keyword(s):  
Cell Injury ◽  
Ischemia Reperfusion ◽  
Circular Rna ◽  
Control Group ◽  
Loss Of Function ◽  
Cardiomyocyte Autophagy ◽  
Myocardial Ischemia Reperfusion ◽  
Injury Research ◽  
Hypoxia Reoxygenation

AbstractAutophagy and apoptosis are involved in myocardial ischemia/reperfusion (I/R) injury. Research indicates that circular RNA HIPK3 (circHIPK3) is crucial to cell autophagy and apoptosis in various cancer types. However, the role of circHIPK3 in the regulation of cardiomyocyte autophagy and apoptosis during I/R remains unknown. Our study aimed to examine the regulatory effect of circHIPK3 during myocardial I/R and investigate its mechanism in cardiomyocyte autophagy and apoptosis. Methods and results. The expression of circHIPK3 was upregulated during myocardial I/R injury and hypoxia/reoxygenation (H/R) injury of cardiomyocytes. To study the potential role of circHIPK3 in myocardial H/R injury, we performed gain-of-function and loss-of-function analyses of circHIPK3 in cardiomyocytes. Overexpression of circHIPK3 significantly promoted H/R-induced cardiomyocyte autophagy and cell injury (increased intracellular reactive oxygen species (ROS) and apoptosis) compared to those in the control group, while silencing of circHIPK3 showed the opposite effect. Further research found that circHIPK3 acted as an endogenous miR-20b-5p sponge to sequester and inhibit miR-20b-5p activity, resulting in increased ATG7 expression. In addition, miR-20b-5p inhibitors reversed the decrease in ATG7 induced by silencing circHIPK3. Conclusions. CircHIPK3 can accelerate cardiomyocyte autophagy and apoptosis during myocardial I/R injury through the miR-20b-5p/ATG7 axis. These data suggest that circHIPK3 may serve as a potential therapeutic target for I/R.

Acute adenosine preconditioning is mediated by p38 MAPK activation in discrete subcellular compartments

2005 ◽  
Vol 288 (3) ◽  
pp. H1359-H1366 ◽  
Author(s):  
Cherry Ballard-Croft ◽  
Gentian Kristo ◽  
Yukihiro Yoshimura ◽  
Easton Reid ◽  
Byron J. Keith ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Adenosine Receptor ◽  
Ischemia Reperfusion ◽  
Mitochondrial Fraction ◽  
Control Group ◽  
Mapk Activation ◽  
Subcellular Compartments ◽  
Sb 203580

Although acute adenosine preconditioning (PC) is well established, the signaling pathways mediating this cardioprotection remain unclear. Because adenosine receptor agonists activate p38 MAPK and this kinase has been implicated in ischemic and pharmacological PC, the purpose of this study was to determine the role of p38 MAPK in acute adenosine receptor PC. The role of p38 MAPK activation in discrete subcellular compartments during ischemia-reperfusion was also determined. The following groups were used in an in vivo rat ischemia-reperfusion model: 1) control (10% DMSO iv), 2) the A1/A2a adenosine receptor AMP-579 (50 μg/kg iv), 3) AMP-579 + the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 μg/kg iv), 4) AMP-579 + the p38 MAPK inhibitor SB-203580 (1 mg/kg iv), and 5) SB-203580 alone. p38 MAPK activation was measured by Western blot analysis in cytosolic, mitochondrial, membrane, and nuclear/myofilament fractions obtained from hearts at preischemic, ischemic, and reperfusion time points. A significant reduction in infarct size was observed with AMP-579 PC, an effect blocked by DPCPX or SB-203580 pretreatment. AMP-579 treatment was associated with a significant increase in p38 MAPK activation in the nuclear/myofilament fraction before ischemia, whereas no activation of this kinase occurred during ischemia or reperfusion. In contrast, p38 MAPK was activated in the mitochondrial fraction by ischemia and in the cytosolic, mitochondrial, and membrane fractions by reperfusion in the control group. SB-203580 blocked the AMP-579-induced increase in phosphorylation of the downstream p38 substrate activating transcription factor-2. These results suggest a role for p38 MAPK activation in discrete subcellular compartments in acute adenosine A1 receptor PC.

scholarly journals The Blockade of Transmembrane Cl- Flux Mitigates I/R-Induced Heart Injury via the Inhibition of Calpain Activity

2015 ◽  
Vol 35 (6) ◽  
pp. 2121-2134 ◽  
Author(s):  
Jian-Ying Zhang ◽  
Feng Wu ◽  
Xiao-Ming Gu ◽  
Zhen-Xiao Jin ◽  
Ling-Heng Kong ◽  
...  
Keyword(s):  
Myocardial Injury ◽  
Caspase 3 ◽  
Ischemia Reperfusion ◽  
Cardiac Injury ◽  
Calpain Activity ◽  
Rat Hearts ◽  
Marked Decline ◽  
Heart Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Injury Area

Aims: The aim of this study was to determine whether calpain is involved in Cl- -induced myocardial ischemia/reperfusion (I/R) injury. Methods: Isolated rat hearts were subjected to either 45 min of global no-flow ischemia followed by reperfusion or successive perfusion with Ca2+ -free KH solution for 3 min and normal KH solution for 30 min, also known as Ca2+ paradox. Results: The hearts in the I/R group exhibited increases in myocardial injury area, LDH release, caspase 3 activity and apoptotic indices and a marked decline in cardiac performance. As was the case regarding the effects of MDL 28170, an inhibitor of calpain, treatment with 5 µM NPPB, 5 µM DIDS and low Cl- significantly attenuated cardiac injury. Moreover, each of the treatments significantly protected against Ca2+ overload-induced injury in the setting of Ca2+ paradox. The Western blot and immunofluorescence data revealed that there was an increase in the percentages of calpain membrane-positive cells and the numbers of fragments resulting from the calpain-mediated proteolysis of α-fodrin in both the I/R and the Ca2+ paradox, indicating that the activation of calpain occurred. More importantly, these effects were mitigated by the blockade of transmembrane Cl- flux, as was accomplished via MDL 28170. Conclusion: Our results provide evidence that the blockade of transmembrane Cl- flux mitigates I/R-induced cardiac injury via the inhibition of calpain activity. They also indicate that intracellular Ca2+ overload regulates calpain activation in the setting of Cl- -induced injury.

scholarly journals The expression and role of β3AR protein in myocardial ischemia/reperfusion in rats

2021 ◽  
Author(s):  
Zi-Long Wang ◽  
Xiao-Chen Sun ◽  
Rong Luo ◽  
Dong-Ye Li ◽  
Hao-Chen Xuan
Keyword(s):  
Myocardial Ischemia ◽  
Protein Expression ◽  
Caspase 3 ◽  
Sham Group ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Sd Rats ◽  
Group I ◽  
Myocardial Ischemia Reperfusion

IntroductionTo explore serum norepinephrine (NE) concentration and β3-adrenoceptor (β3AR) protein expression at different times during myocardial ischemia/reperfusion (I/R) and examine the role of β3AR in I/R.Material and methods28 Sprague-Dawley (SD) rats were randomly divided into one sham group and six I/R groups. The rats in the I/R groups were subjected to ischemia for 45 minutes. After reperfusion, the serum NE concentration and the β3AR protein expression in the myocardial tissue of the left ventricular injury region were detected. Another 18 SD rats were randomly divided into a sham group, I/R groups, and I/R + BRL37344 group.ResultsCompared with the sham group, the serum NE concentration of rats in the I/R groups significantly increased at 6 hours (P < 0.001). The serum NE concentration and myocardial β3AR protein expression were both highest at 72 hours. Compared with the sham group, the expressions of the pro-apoptotic proteins Bax and cleaved caspase-3 after I/R were significantly increased (P < 0.01, P < 0.001, respectively), and the expression of anti-apoptotic protein Bcl-2 was significantly decreased (P < 0.01). Compared with I/R groups, the expressions of Bax and cleaved caspase-3 in the I/R + BRL37344 group were significantly decreased (P < 0.05, P < 0.01, respectively).ConclusionsWith the prolongation of myocardial I/R in rats, serum NE concentration and β3AR protein expression showed a significant increase trend and reached a peak at 72 hours. Specific β3AR agonist BRL37344 can reduce myocardial I/R injury in vivo in rats, alleviate apoptosis, reduce infarct size, and improve cardiac function.

scholarly journals The cardioprotective effect of intralipid in decreasing the ischemic insults during off-pump coronary artery revascularization

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Maha Sadek El Derh ◽  
Samar Mohamed Abdel Twab ◽  
Mohamed Elgouhary
Keyword(s):  
Coronary Artery ◽  
Cardiac Index ◽  
Reperfusion Injury ◽  
Troponin I ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Myocardial Infarct Size ◽  
Off Pump ◽  
Coronary Artery Revascularization

Abstract Background Off pump coronary artery revascularization (OPCAB) surgeries have benefits over the conventional on pump cardiac surgery, because it avoids the trauma caused by cardiopulmonary bypass (CPB) and minimize aortic manipulation. However, some disadvantages of OPCAB include the concern of ineffective coronary revascularization. Some drugs have shown the ability to protect the myocardium in different studies, by different methods. The usage of intralipid has been shown to make a better functional recovery of the cardiac muscles and help to decrease the myocardial infarct size, it shortens the action potential time, which show polyunsaturated fatty acids diets mechanism as an antiarrhythmic drug, and are associated with low incidence of coronary artery disease. Methods We divided patients into two groups according to the randomization envelopes: intralipid group (group A) received 1.5 ml/kg intralipid 20% through central venous line after sternotomy over 1 h and during infusion, blood pressure, heart rate, and temperature were monitored all through the infusion time. Control group (group B) received normal saline 0.9% in the same volume over the same duration. Results This study showed that infusion of 1.5 ml/kg intralipid after sternotomy in off pump coronary artery revascularization given as preconditioning agent improve the myocardial ischemia reperfusion injury, decrease the need for high doses of nor adrenaline infusion after revascularization, earlier normalization in troponin levels starting 24 h after surgery and higher values of cardiac index were measured in ICU using PICCO. Conclusions This study showed the benefits of infusion of 1.5 ml/kg of intralipid after sternotomy, in preconditioning during OPCABG. Preconditioning with intralipid proved to decrease reperfusion injury in myocardium expressed by improvement in cardiac functions (EF and cardiac index) and normalization of specific cardiac marker (cardiac troponin I).

scholarly journals The protective role of CsNPs and CurNPs against DNA damage, oxidative stress, and histopathological and immunohistochemical alterations induced by hydroxyapatite nanoparticles in male rat kidney

2019 ◽  
Vol 8 (5) ◽  
pp. 741-753 ◽  
Author(s):  
Israa F. Mosa ◽  
Mokhtar I. Yousef ◽  
Maher Kamel ◽  
Osama F. Mosa ◽  
Yasser Helmy
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Biological Effects ◽  
Male Rats ◽  
Nuclear Antigen ◽  
Male Rat ◽  
Control Group ◽  
Renal Tubules ◽  
Hydroxyapatite Nanoparticles

Abstract Hydroxyapatite nanoparticles (HAP-NPs) are an inorganic component of natural bone and are mainly used in the tissue engineering field due to their bioactivity, osteoconductivity, biocompatibility, non-inflammatory, and non-toxicity properties. However, the current toxicity data for HAP-NPs regarding human health are limited, and only a few results from basic studies have been published. Therefore, the present study was designed to investigate the beneficial role of chitosan nanoparticles (CsNPs) and curcumin nanoparticles (CurNPs) in alleviating nephrotoxicity induced by HAP-NPs in male rats. The results showed that HAP-NPs caused a reduction in antioxidant enzymes and induced lipid peroxidation, nitric oxide production and DNA oxidation. Moreover, HAP-NP administration was associated with intense histologic changes in kidney architecture and immunoreactivity to proliferating cell nuclear antigen (PCNA). However, the presence of CsNPs and/or CurNPs along with HAP-NPs reduced the levels of oxidative stress through improving the activities of antioxidant enzymes. Also, the rats administered the nanoparticles showed a moderate improvement in glomerular damage which matched that of the control group and showed mild positive reactions to PCNA–ir in glomeruli and renal tubules in the cortical and medullary portions. These novel insights confirm that the presence of chitosan and curcumin in nanoforms has powerful biological effects with enhanced bioactivity and bioavailability phenomena compared to their microphase counterparts. Also, they were able to ameliorate the nephrotoxicity induced by HAP-NPs.

scholarly journals Hydrogen sulfide-mediated cardioprotection against ischemia reperfusion is linked to KATP channel for mitochondrial preservation but not for its distinct preference on interfibrillar mitochondria

2019 ◽  
Vol 14 (2) ◽  
pp. 107-115 ◽  
Author(s):  
Priyadharshini Chandrasekaran ◽  
Sriram Ravindran ◽  
Sri Rahavi Boovarahan ◽  
Gino A. Kurian
Keyword(s):  
Hydrogen Sulfide ◽  
Reperfusion Injury ◽  
Katp Channel ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Rat Hearts ◽  
Significant Difference ◽  
Interfibrillar Mitochondria ◽  
Subsarcolemmal Mitochondria

Hydrogen sulfide has been shown to protect  myocardium against ischemia-reperfusion injury by preserving interfibrillar mitochondria functional activi-ties than subsarcolemmal mitochondria. In this study, the role of the KATP channel in modulating the mitochondrial subpopulations during the cardioprotection mediated by NaSH (H2S donor) was investigated. Isolated rat hearts were treated with mitochondrial KATP channel closer glibenclamide (10 μM)/opener diazoxide (0.8 mM) via Langendorff perfusion apparatus before ischemia-reperfusion. The results showed that NaSH pre-conditioning in presence of glibenclamide significantly improved cardiac recovery without any significant difference between interfibrillar mitochondria and subsarcolemmal mitochondria.  In conclusion, targeting KATP channel may not be good option to target interfibrillar mitochondria/subsarcolemmal mitochondria against ischemia-reperfusion injury.

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